**Executive Summary:**
The Central Drugs Standard Control Organisation is examining the feasibility of replacing the Draize test on rabbits with alternative methods for eye and skin irritation/corrosion testing. A committee has been formed and stakeholders are requested to provide feedback on the feasibility, validation, and preparedness of Indian laboratories for adopting alternative testing methods. Comments are requested within two weeks from the date of the notice (Q1OG.G.......).
**Key Points / Main Content:**
* **Objective:** To explore replacing the Draize test (rabbit eyes and skin) with alternative methods for testing eye and skin irritation or corrosion.
* **Committee Formation:** A committee has been constituted to provide recommendations for necessary action.
* **International Trends:** Acknowledges the international trend towards replacing animal testing with alternatives.
* **Feasibility Assessment:** The adoption of alternative methods in India will be considered after assessing feasibility, validation, and preparedness of Indian laboratories.
* **Stakeholder Feedback:**
* Feedback is being sought from laboratories involved in preclinical toxicity tests (public and private sectors) and the pharmaceutical industry.
* Stakeholders are requested to provide comments on the preparedness for alternative testing methods and the resources required for capacity building.
* **Feedback Proforma:** A feedback proforma is included to gather data from stakeholders regarding their current testing practices (Draize test usage, alternative method capabilities) and preparedness for transitioning to alternative methods.
* **Information Requested:** The feedback form requests details on the stakeholder organization, current use of Draize tests, experience with alternative in-vitro tests (OECD TG 430, 431, 435, 439, 460, 437, 438, 491, 492, 442c, 442d, hCLAT), and preparedness for replacing in-vivo tests with in-vitro methods.
* **Deadline:** Stakeholders are requested to provide their comments within two weeks.
**Impact Analysis:**
**Testing Laboratories (Public and Private):**
* *Impact:* Need to assess their current capabilities, identify gaps in adopting alternative testing methods, and estimate the resources required for capacity building.
* *Action Required:* Provide feedback to the Drugs Controller General of India within two weeks, detailing their current testing practices, experience with alternative methods, and preparedness for transitioning to alternative methods, including the resources or time needed.
**Pharmaceutical Industry:**
* *Impact:* May need to adapt their testing protocols and potentially invest in new equipment or training to align with alternative testing methods, if implemented.
* *Action Required:* Provide feedback to the Drugs Controller General of India within two weeks, regarding their perspectives on the feasibility and impact of replacing the Draize test with alternative methods.
**Related Organizations:**
* *Impact:* These organisations are undefined in the text but are nonetheless required to provide feedback.
* *Action Required:* Provide feedback to the Drugs Controller General of India within two weeks, regarding their perspectives on the feasibility and impact of replacing the Draize test with alternative methods.
Key Entities Referenced
Draize test: A test applied on Rabbit eyes and skin for testing of eyes and skin irritation or corrosion, the document discusses replacing it with alternative methods.
Central Drugs Standard Control Organisation: An organisation under Directorate General of Health Services, mentioned as the office responsible for the notification.
Drugs Controller General India: The title of the signatory authority, Dr. G.N. Singh.
ScheduleY: A requirement related to drug testing, mentioned in the context of international trends and alternative testing methods.
OECD guidelines: Guidelines from the Organisation for Economic Co-operation and Development that have suggested the use of alternative methods for testing.
US FDA: United States Food and Drug Administration, has initiated the process of use of alternative methods.
European Union: A political and economic union, has initiated the process of use of alternative methods.
Drugs and Cosmetics Act: Indian Legislation related to drugs and cosmetics
F. No. DCGI/Misc/2016-61
Directorate General of Health Services
Central Drugs Standard Control Organisation
Office of Drugs Controller General India.
FDA Bhawan, Kotla Road,
New Delhi-110002
Dated .Q1-OG.-\G.......
NOTICE
In order to examine the feasibility to replace Draize test which is applied on Rabbit eyes and
skin by alternative methods for testing of eyes and skin irritation or corrosion. A committee
has been constituted to give its recommendation for taking necessary action in the matter.
The committee in its first meeting held on 23" May, 2016 deliberated the issue and perused
the related literature applicable globally vis-a-vis Schedule-Y requirement. The committee
opined that as there is international trend towards replacing tests on animals with alternatives
it may be considered in Indian context, after obtaining assessment of feasibility, validation,
preparedness of Indian laboratories etc.
It is further decided to seek the feedback/opinion from different stakeholders viz. laboratories
involved in carrying out preclinical toxicity tests from public, private sector and related
organisation from pharmaceutical industry before taking the final decision in the matter.
Points of discussion of minutes of meeting and Feedback Proforma for obtaining comments
are attached for ready reference.
In view of above all the stake holders including testing laboratories are requested to kindly
provide their comments to the undersigned within a period of two week to enable this office
to take necessary action in the matter.
(Dr. G,/N. Singh)
Drugs Controller/General (I)Points of Discussion of Minutes of Meeting
The committee perused the related literature applicable globally vis-a-vis
Schedule-Y requirement. It noted that several alternative tests are being
evolved and validated to different stages. The OECD guidelines have
also suggested use of alternative methods. The committee also noted
that US FDA and European Union have initiated the process of use of
alternative methods.
The committee opined that as there is international trend towards
replacing tests on animals with alternatives it may be considered in
Indian context, after obtaining assessment of feasibility, validation,
preparedness of Indian laboratories etc.
The main contentions are; are Indian pre clinical testing laboratories
equipped for such change? have the alternative methods been validated
particularly in India?, do we have adequate number of laboratories to
undertake the toxicity testing of all required substances by alternative
methods ?. If the answer is NO or PARTIAL, how much time and what
efforts will be required for capacity building for using alternate
methods?
In this regard, it was therefore decided to seek the feedback/opinion
from different stakeholders viz. laboratories involved in carrying out
preclinical toxicity tests from public, private sector and related
organisation from pharmaceutical industry on the above issue. The
committee decided that data in this connection may be obtained in the
“Feedback from stakeholders”.Feedback proforma from stakeholders
(Response requested in 15 days)
Government of India is considering to replace the above said tests with alternative
methods for eye irritation test in rabbits and Dermal toxicity tests for skin
irritation/corrosion tests in rabbits and skin sensitization in guinea pigs and mice by
alternative methods with respect to the approval of new drugs and therefore
examining the feasibility of such replacement in Indian situation. In this regard, you
are requested to provide the following information-
1. Name of the stake holder / Organization:
2: Address
Telephone
FAX
E-mail
Name of the person and designation submitting the profile.....:
Whether your facility is currently conducting / has experience with Draize test/ocular
toxicity test and skin irritation/corrosion tests in rabbits and skin sensitisation test in
guinea pigs or mice?
If your facility conducts the eye and skin irritation tests on rabbit then, for what type of
following pharmaceuticals/chemicals are the tests conducted? (Please provide Average
number of tests done in last year)
a. Pharmaceuticals: NO—————————_/year
b. Chemicals /pesticides: —No————————_/year
c. Chemicals / surfactants / environmental pollutants No: /year
To which regulatory agency(ies), the reports are submitted?
Do you have facilities to carry out following in-vitro tests which have been adopted by the
OECD?
A. Tests for skin irritation
a. OECD TG 430: /n vitro trans cutaneous electrical resistance test method for
skin corrosion Y/N
b. OECD TG 431: /n vitro reconstructed human epidermis test method for skin
corrosion. YIN
c. OECD TG 435: /n vitro membrane barrier test method for skin corrosion. Y/Nd. OECD TG 4339: In vitro reconstructed human epidermis test method for skin
irritation. Y/N
e. OECD Guidance Document 203: guidance document on an IATA for skin
corrosion and irritation. Y/N
B. Tests for Eye irritation:
a. OECD TG 460: Fluoresce in leakage test method for identifying ocular
corrosives and severe irritants. Y/N
b. OECD TG 437: Bovine corneal Opacity and permeability test method. Y/N
c. OECD TG 438: Isolated chicken eye test method. Y/N
d. OECD TG 491: Short time exposure in vitro test method for identifying
(i) chemicals inducing serious eye damage. Y/N
(ii) chemicals not requiring classification for eye irritation or serious eye damage.
YIN
OECD TG 492: Reconstructed human cornea-like epithelium (RhCE) test
method for identifying chemicals not requiring classification and labelling for eye
irritation or serious eye damage. Y/N
f. Draft OECD TG: Cytosensor microphysiometer method: An in vitro Method for
Identifying Ocular 3 Corrosive and Severe Irritant Chemicals as well as
Chemicals not classified as Ocular Irritants. The cytosensor microphysiometer
method is also recommended by the European Union Reference Laboratory for
alternatives to animal testing to differentiate water-soluble ocular corrosives and
severe irritants and non-irritants in a top-down and bottom-up approaches,
respectively. Y/N
C. Test for Skin Sensitisation
OECD TG 442c: In Chemico Skin Sensitisation — Direct Peptide Reactivity
Assay (DPRA). Y/N
b. OECD TG 442d: In Vitro Skin Sensitisation — ARE-Nrf2 Luciferase Test Method
(Keratino SensTM). Y/N
OECD draft TG: Human Cell Line Activation Test (h-CLAT) ; final test guideline
expected to be published later in 2016). Y/N
8. In case the eye and skin irritation tests on rabbits are replaced in Chapter-3 of
Schedule-Y of Drugs and Cosmetics Act, with alternative in-vitro and ex-vivo
methods, do you have preparedness? Y/N
a. If ‘No, what will be the time period requirement?
9. Any other Comment?